The Staged Treatment in Early Psychosis Study

NCT02751632 | Completed Phase 3 DMC

• 2 other identifiers: 2015.1731U01MH105258-01
• Study Type: interventional
• Target: 342
• Locations: 1 country
• Sites: 5

Brief Summary

A sequential multistage randomised clinical trial (SMART) to produce evidence to guide a step-wise clinical approach for the treatment of ultra high risk patients and reduction of risk for psychosis and other deleterious clinical and/or functional outcomes.

Conditions

Psychotic Disorders; Personality Disorders; Clinical High Risk

Keywords

Ultra High Risk of Psychosis; Prodrome; Clinical High Risk of Psychosis

Outcome Measures

Primary Outcomes (1)

• Global Functioning Scale Score

  To test the effect of a sequential treatment approach consisting of SPS/SPS and SPS/CBCM on functioning levels of UHR patients.

  6 months from baseline (end of Step 2)

Secondary Outcomes (7)

• Global Functioning Scale Score

  12 months from baseline (end of Step 3)

• Comprehensive Assessment of At Risk Mental State score

  12 and 24 months from baseline

• Comprehensive Assessment of At Risk Mental State score

  1.5, 6, 12 and 24 months from baseline

• Scale for Assessment of Negative Symptoms score

  1.5, 6, 12 and 24 months from baseline

• Comprehensive Assessment of At Risk Mental State score

  During the first 12 months from baseline.

Study Arms (7)

Step 1-Regular SPS Therapy

EXPERIMENTAL

Support and Problem Solving Therapy delivered to all study participants over a six-week period with a minimum of three sessions.

Behavioral: Support and Problem Solving Therapy

Responders- Monthly SPS Therapy

EXPERIMENTAL

Participants are randomised to receive monthly Support and Problem Solving Therapy for up to 12 months.

Behavioral: Support and Problem Solving Therapy

Responders- 3-monthly monitoring

EXPERIMENTAL

Participants are randomised to be monitored for risk every 3 months for up to 12 months.

Behavioral: 3-monthly monitoring

Step 2- Regular SPS Therapy

EXPERIMENTAL

Participants are randomised to receive regular sessions of Support and Problem Solving Therapy, with a minimum of six sessions delivered over an 18-week period.

Behavioral: Support and Problem Solving Therapy

Step 2- Regular CBCM

EXPERIMENTAL

Participants are randomised to receive regular sessions of Cognitive Behavioural Case Management, with a minimum of six sessions delivered over an 18-week period.

Behavioral: Cognitive Behavioural Case Management

Step 3- Regular CBCM + Fluoxetine

EXPERIMENTAL

Participants are randomised to receive either Cognitive Behavioural Case Management plus an antidepressant medication for six months .

Behavioral: Cognitive Behavioural Case Management; Drug: Fluoxetine

Step 3- Regular CBCM+ placebo

PLACEBO COMPARATOR

Participants are randomised to receive Cognitive Behavioural Case Management plus placebo medication for six months.

Behavioral: Cognitive Behavioural Case Management; Drug: Placebo

Interventions

Support and Problem Solving Therapy BEHAVIORAL

Support and Problem Solving Therapy involves providing participants with emotional support and helping them to resolve their problems in day-to-day life.

Also known as: SPS

Responders- Monthly SPS Therapy; Step 1-Regular SPS Therapy; Step 2- Regular SPS Therapy

Cognitive Behavioural Case Management BEHAVIORAL

CBCM has a number of different elements including: strategies to help with stress management; therapy that targets thinking and behavioural patterns; practical assistance, as well as yoga and mindfulness.

Also known as: CBCM

Step 2- Regular CBCM; Step 3- Regular CBCM + Fluoxetine; Step 3- Regular CBCM+ placebo

Fluoxetine DRUG

Participants will commence on 1 capsule of fluoxetine 20 mg, to be taken in the morning. The medication can be increased to fluoxetine 40 mg daily if there has been a poor clinical response after the first 6 weeks of treatment.

Also known as: Anti-depressant medication

Step 3- Regular CBCM + Fluoxetine

Placebo DRUG

Participants will commence on 1 capsule of the placebo pill, to be taken in the morning. The medication can be increased to 2 placebo capsules if there has been a poor clinical response after the first 6 weeks of treatment.

Also known as: Inactive Medicine

Step 3- Regular CBCM+ placebo

3-monthly monitoring BEHAVIORAL

Study participants will be contacted on a 3-monthly basis by a study clinician who will be assessing the participant's risk.

Responders- 3-monthly monitoring

Eligibility Criteria

• Age: 12 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 12 -25 years (inclusive) at entry.
• Ability to speak adequate English (for assessment purposes).
• Ability to provide informed consent.
• Meeting one or more Ultra High Risk for psychosis groups as defined below:
• Group 1: Vulnerability Group
• Family history of psychosis in first degree relative OR Schizotypal Personality Disorder (as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM) IV in identified patient
• AND
• Drop in Functioning:
• Recency: Change in functioning occurred within last year Impact: Social and Occupational Functioning Assessment Scale (SOFAS) score at least 30% below previous level of functioning and sustained for at least one month.
• Sustained low functioning:
• Recency: For the past 12 months or longer Impact: SOFAS score of 50 or less.
• Group 2: Attenuated Psychotic Symptoms Group 2a) Subthreshold intensity:
• Intensity: Global Rating Scale Score of 3-5 on Unusual Thought Content subscale, 3-5 on Non-Bizarre Ideas subscale, 3-4 on Perceptual Abnormalities subscale and/or 4-5 on Disorganised Speech subscales of the Comprehensive Assessment of At Risk Mental States (CAARMS).
• Frequency: Frequency Scale Score of 3-6 on Unusual Thought Content, Non-Bizarre Ideas, Perceptual Abnormalities and/or Disorganised Speech subscales of the CAARMS
• Duration: symptoms present for at least one week

You may not qualify if:

• Past history of a psychotic episode of one week or longer, whether treated with antipsychotic medications or not.
• Attenuated psychotic symptoms only present during acute intoxication.
• Organic brain disease known to cause psychotic symptoms, e.g. temporal lobe epilepsy.
• Any metabolic, endocrine or other physical illness, e.g. thyroid disease, with known neuropsychiatric consequences.
• Diagnosis of a serious developmental disorder, e.g. Severe Autism Spectrum Disorder.
• Premorbid Intelligence Quotient (IQ) \<70 and a documented history of developmental delay or intellectual disability.
• Current or previous SCID diagnosis of Bipolar I.

Sponsors & Collaborators

• Orygen: lead
• National Institute of Mental Health (NIMH): collaborator
• University of California, Davis: collaborator
• University of California, San Francisco: collaborator

Study Sites (5)

Headspace

Craigieburn, Victoria, 3064, Australia

Location

Headspace

Glenroy, Victoria, 3046, Australia

Location

Orygen Youth Health Clinical Program

Melbourne, Victoria, 3052, Australia

Location

Headspace

Sunshine, Victoria, 3020, Australia

Location

Headspace

Werribee, Victoria, 3030, Australia

Location

Related Publications (1)

• McGorry PD, Mei C, Amminger GP, Yuen HP, Kerr M, Spark J, Wallis N, Polari A, Baird S, Buccilli K, Dempsey SA, Ferguson N, Formica M, Krcmar M, Quinn AL, Mebrahtu Y, Ruslins A, Street R, Wannan C, Dixon L, Carter C, Loewy R, Niendam TA, Shumway M, Nelson B. A Sequential Adaptive Intervention Strategy Targeting Remission and Functional Recovery in Young People at Ultrahigh Risk of Psychosis: The Staged Treatment in Early Psychosis (STEP) Sequential Multiple Assignment Randomized Trial. JAMA Psychiatry. 2023 Sep 1;80(9):875-885. doi: 10.1001/jamapsychiatry.2023.1947.

  PMID: 37378974 DERIVED

MeSH Terms

Conditions

Psychotic Disorders; Personality Disorders

Interventions

Palliative Care; Fluoxetine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services; Propylamines; Amines; Organic Chemicals

Study Officials

• Patrick McGorry, MD, PhD

  Orygen Youth Research Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2016
• First Posted: April 26, 2016
• Study Start: April 1, 2016
• Primary Completion: July 1, 2019
• Study Completion: May 1, 2022
• Last Updated: October 2, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5)